Advanced age is a risk factor for many age related disorders, and it may enhance susceptibility for disease in the next generation. The recent joint publication of the DZNE Bonn and the German Mouse Clinic reports a reduced life span and an exacerbated development of aging traits in old father offspring compared to young father offspring.

The scientists assessed two groups of mice that included the offspring generation of young and old fathers, respectively. Young mouse-fathers were mated at an age of four months – an age that mice are considered as young adults – while the old fathers with an age of at least 21 months were already seniors. The mouse-mothers were all four months old. All offspring grew up under the same living conditions and never had contact with their fathers. Rodents from both groups were examined at the age of 6 and 19 months, respectively.

The phenotyping analysis of the old father offspring mice revealed alterations in learning and memory and in addition, metabolic and immunological changes that could contribute to age related pathologies. Paternal age effects were also evident with regards to lifespan: Offspring mice of young fathers showed a median lifespan about two months longer than children of old fathers. The scientists discovered alterations in the sperm of the fathers with regards to epigenetic marks of the genome carried by sperm. In both, sperm from aging males and old father offspring tissue, differentially methylated promoters enriched for genes involved in the regulation of evolutionarily conserved longevity pathways were identified.These findings link inherited alterations in longevity pathways to intergenerational effects of aging in old father offspring mice.